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Genetic polymorphisms influence gene expression of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement

  • Erika Calvano Küchler
  • Agnes Schröder
  • Paola Corso
  • Rafaela Scariot
  • Gerrit Spanier
  • Peter Proff
  • Christian KirschneckEmail author
Original Article


Genetic polymorphisms could be involved in the individual rate of OTM (orthodontic tooth movement) corresponding to the clinical phenomenon of “slow movers” and “fast movers”. This study evaluated, if genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6 are associated with the expression of RANKL, OPG, COX2 and IL6 by human periodontal ligament (hPDL) fibroblasts during OTM. Primary hPDL fibroblasts from periodontal connective tissue of teeth extracted from 57 human subjects for medical reasons were collected, isolated, cultivated and characterized. To simulate orthodontic forces in PDL pressure areas, a physiological compressive force of 2 g/cm2 was applied to the hPDL fibroblasts under cell culture conditions at 70% confluency for 48 h, using a glass disc. Thereafter we analysed relative expression of RANKL, OPG, COX2 and IL6 by RT-qPCR. We also performed genotyping analysis of seven genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6. Relative gene expression was compared among the genotypes. The genotype TT in polymorphism rs9594738 (RANKL) had a higher RANKL expression in the recessive model (p = 0.021; TT vs. CT + CC). For polymorphism rs9594738 (RANKL), in the recessive model, TT was associated with a higher RANKL/OPG expression ratio (p = 0.013; TT vs. CT + CC). In the dominant model, GG genotype in rs5275 (COX2) was associated with a lower gene expression of COX2 (p = 0.04; GG vs. AA + AG). Genetic polymorphisms in genes associated with OTM affect the relative force-induced upregulation of these genes in hPDL fibroblasts.


Genetic polymorphism Orthodontics Periodontal ligament Bone Connective tissue 



This study was funded by the Bavarian University Centre for Latin America BAYLAT (Grant ID: Kirschneck 12/2017) and by the São Paulo Research Foundation (FAPESP) (Grant ID: Küchler 2015/06866-5).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Approval for the collection and usage of hPDL fibroblasts was obtained from the ethics committee of the University of Regensburg, Germany [approval number 12-170-0150]. This article does not contain any studies with animals.

Supplementary material

10266_2019_475_MOESM1_ESM.pdf (324 kb)
Supplementary material 1 Raw genotype and phenotype gene expression data of all individual subjects investigated (PDF 323 kb)


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Copyright information

© The Society of The Nippon Dental University 2019

Authors and Affiliations

  1. 1.Department of Pediatric Dentistry, School of Dentistry of Ribeirão PretoUniversidade de São PauloRibeirão PretoBrazil
  2. 2.Department of OrthodonticsUniversity of RegensburgRegensburgGermany
  3. 3.Department of Oral and Maxillofacial SurgeryUniversidade PositivoCuritibaBrazil
  4. 4.Department of Cranial and Maxillofacial SurgeryUniversity of RegensburgRegensburgGermany

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